Glimepiride

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Drugbox Glimepiride is an antidiabetic medication within the sulfonylurea class, primarily prescribed for the management of type 2 diabetes.<ref name=AHFS2019/><ref name=BNF76>Template:Cite book</ref> It is regarded as a second-line option compared to metformin, due to metformin's well-established safety and efficacy.<ref name=AHFS2019/> Use of glimepiride is recommended in conjunction with lifestyle modifications such as diet and exercise.<ref name=AHFS2019/> It is taken by mouth,<ref name=AHFS2019/> reaching a peak effect within three hours and lasting for about a day.<ref name=AHFS2019/>

Common side effects include headache, nausea, and dizziness.<ref name=AHFS2019/> Serious side effects may include low blood sugar.<ref name=AHFS2019/> Use during pregnancy and breastfeeding is not recommended.<ref name=Preg2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It works predominantly by increasing the amount of insulin released from the pancreas.<ref name=AHFS2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is classified as a second-generation sulfonylurea.<ref name="pmid15531188">Template:Cite journal</ref>

Glimepiride was patented in 1979 and approved for medical use in 1995.<ref>Template:Cite book</ref> It is available as a generic medication.<ref name=BNF76/> In 2022, it was the 64th most commonly prescribed medication in the United States, with more than 10Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

File:Glimepiride 2 MG Oral Tablet.jpg

Two generic oral tablets of glimepiride, 2 mg each

Glimepiride is indicated to treat type 2 diabetes; its mode of action is to increase insulin secretion by the pancreas. However it requires adequate insulin synthesis as prerequisite to treat appropriately. It is not used for type 1 diabetes because in type 1 diabetes the pancreas is not able to produce insulin.<ref name="ncbi.nlm.nih.gov">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Contraindications

Its use is contraindicated in patients with hypersensitivity to glimepiride or other sulfonylureas.

Adverse effects

Side effects from taking glimepiride include gastrointestinal tract (GI) disturbances, occasional allergic reactions, and rarely blood production disorders including thrombocytopenia, leukopenia, and hemolytic anemia. In the initial weeks of treatment, the risk of hypoglycemia may be increased. Alcohol consumption and exposure to sunlight should be restricted because they can worsen side effects.<ref name="ncbi.nlm.nih.gov"/>

Interactions

Nonsteroidal anti-inflammatory drugs (such as salicylates), sulfonamides, chloramphenicol, coumadin and probenecid may potentiate the hypoglycemic action of glimepiride. Thiazides, other diuretics, phothiazides, thyroid products, oral contraceptives, and phenytoin tend to produce hyperglycemia.

Mechanism of action

Like all sulfonylureas, glimepiride acts as an insulin secretagogue.<ref name="pmid18378631">Template:Cite journal</ref> It lowers blood sugar by stimulating the release of insulin by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors.

Not all secondary sulfonylureas have the same risk of hypoglycemia. Glibenclamide (glyburide) is associated with an incidence of hypoglycemia of up to 20–30%, compared to as low as 2% to 4% with glimepiride. Glibenclamide also interferes with the normal homeostatic suppression of insulin secretion in reaction to hypoglycemia, whereas glimepiride does not. Also, glibenclamide diminishes glucagon secretion in reaction to hypoglycemia, whereas glimepiride does not.<ref name=G&G>Template:Cite book</ref>

Pharmacokinetics

Gastrointestinal absorption is complete, with no interference from meals. Significant absorption can occur within one hour, and distribution is throughout the body, 99.5% bound to plasma protein. Metabolism is by oxidative biotransformation, it is hepatic and complete. First, the medication is metabolized to M₁ metabolite by CYP2C9. M₁ possesses about Template:Frac of pharmacological activity of glimepiride, yet it is unknown if this results in clinically meaningful effect on blood glucose. M₁ is further metabolized to M₂ metabolite by cytosolic enzymes. M₂ is pharmacologically inactive. Excretion in the urine is about 65%, and the remainder is excreted in the feces.